Objective To investigate the significance of serum interleukin 17 (IL-17), platelet-to-lymphocyte ratio (PLR), and vascular endothelial growth factor (VEGF) expression and their correlation with disease progression in hepatitis B virus (HBV) infected patients. Method Eighty-two HBV-infected patients admitted from June 2022 to March 2024 were selected as the study group, and according to the degree of disease progression, the 82 patients were divided into 37 cases of group A (chronic hepatitis B), 24 cases of group B (compensated cirrhosis), and 21 cases of group C (decompensated cirrhosis), and 30 healthy medical check-ups were selected as the control group. In addition HBV-infected patients were classified into 18 cases of negative group (<1.0×105copy/ml), 26 cases of low load group (1.0×105~1.0×108copy/ml) and 38 cases of high load group (>1.0×108copy/ml) according to serum HBV DNA load. Serum IL-17, PLR, VEGF expression levels and HBV DNA load were detected in all subjects, and the correlation between serum IL-17, PLR, VEGF expression levels and disease progression was analysed. Result The serum IL-17, PLR, and VEGF expression levels of patients in the study group were significantly higher than those in the control group (P<0.05), and the serum IL-17, PLR, and VEGF levels of patients in group C were significantly higher than those in group B and group A, whereas those in group B were significantly higher than those in group A. The serum IL-17, PLR, and VEGF levels of patients in the high-load group were significantly higher than those in the low-load and negative groups, while serum IL-17, PLR, and VEGF levels in patients in the low-load group were significantly higher than those in the negative group (all P<0.05), Pearson correlation coefficient analyses of elevated serum IL-17, PLR, and VEGF levels were positively correlated with HBV DNA load, compensated cirrhosis, and decompensated cirrhosis (P<0.05), and multifactor Logistic regression analysis showed that elevated IL-17, PLR, and VEGF expression levels were all risk factors for disease progression (P<0.05). The AUCs for the combined diagnosis of compensated cirrhosis and decompensated cirrhosis using serum IL-17, PLR, and VEGF are 0.823 and 0.835, respectively. Conclusion As important biomarkers reflecting HBV infection and disease progression, changes in the levels of serum IL-17, PLR and VEGF are closely related to HBV DNA load, compensated cirrhosis and decompensated cirrhosis. By monitoring the changes in the levels of these cytokines, it helps us to more accurately assess the severity of the disease and prognostic risk of HBV-infected patients, and provides a valuable reference basis for clinical diagnosis and treatment.